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Archive for the ‘interventional oncology’ Category


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

A mutated gene called RAS gives rise to a signalling protein Ral which is involved in tumour growth in the bladder. Many researchers tried and failed to target and stop this wayward gene. Signalling proteins such as Ral usually shift between active and inactive states.

 

So, researchers next tried to stop Ral to get into active state. In inacvtive state Ral exposes a pocket which gets closed when active. After five years, the researchers found a small molecule dubbed BQU57 that can wedge itself into the pocket to prevent Ral from closing and becoming active. Now, BQU57 has been licensed for further development.

 

Researchers have a growing genetic data on bladder cancer, some of which threaten to overturn the supposed causes of bladder cancer. Genetics has also allowed bladder cancer to be reclassified from two categories into five distinct subtypes, each with different characteristics and weak spots. All these advances bode well for drug development and for improved diagnosis and prognosis.

 

Among the groups studying the genetics of bladder cancer are two large international teams: Uromol (named for urology and molecular biology), which is based at Aarhus University Hospital in Denmark, and The Cancer Genome Atlas (TCGA), based at institutions in Texas and Boston. Each team tackled a different type of cancer, based on the traditional classification of whether or not a tumour has grown into the muscle wall of the bladder. Uromol worked on the more common, earlier form, non-muscle-invasive bladder cancer, whereas TCGA is looking at muscle-invasive bladder cancer, which has a lower survival rate.

 

The Uromol team sought to identify people whose non-invasive tumours might return after treatment, becoming invasive or even metastatic. Bladder cancer has a high risk of recurrence, so people whose non-invasive cancer has been treated need to be monitored for many years, undergoing cystoscopy every few months. They looked for predictive genetic footprints in the transcriptome of the cancer, which contains all of a cell’s RNA and can tell researchers which genes are turned on or off.

 

They found three subgroups with distinct basal and luminal features, as proposed by other groups, each with different clinical outcomes in early-stage bladder cancer. These features sort bladder cancer into genetic categories that can help predict whether the cancer will return. The researchers also identified mutations that are linked to tumour progression. Mutations in the so-called APOBEC genes, which code for enzymes that modify RNA or DNA molecules. This effect could lead to cancer and cause it to be aggressive.

 

The second major research group, TCGA, led by the National Cancer Institute and the National Human Genome Research Institute, that involves thousands of researchers across USA. The project has already mapped genomic changes in 33 cancer types, including breast, skin and lung cancers. The TCGA researchers, who study muscle-invasive bladder cancer, have looked at tumours that were already identified as fast-growing and invasive.

 

The work by Uromol, TCGA and other labs has provided a clearer view of the genetic landscape of early- and late-stage bladder cancer. There are five subtypes for the muscle-invasive form: luminal, luminal–papillary, luminal–infiltrated, basal–squamous, and neuronal, each of which is genetically distinct and might require different therapeutic approaches.

 

Bladder cancer has the third-highest mutation rate of any cancer, behind only lung cancer and melanoma. The TCGA team has confirmed Uromol research showing that most bladder-cancer mutations occur in the APOBEC genes. It is not yet clear why APOBEC mutations are so common in bladder cancer, but studies of the mutations have yielded one startling implication. The APOBEC enzyme causes mutations early during the development of bladder cancer, and independent of cigarette smoke or other known exposures.

 

The TCGA researchers found a subset of bladder-cancer patients, those with the greatest number of APOBEC mutations, had an extremely high five-year survival rate of about 75%. Other patients with fewer APOBEC mutations fared less well which is pretty surprising.

 

This detailed knowledge of bladder-cancer genetics may help to pinpoint the specific vulnerabilities of cancer cells in different people. Over the past decade, Broad Institute researchers have identified more than 760 genes that cancer needs to grow and survive. Their genetic map might take another ten years to finish, but it will list every genetic vulnerability that can be exploited. The goal of cancer precision medicine is to take the patient’s tumour and decode the genetics, so the clinician can make a decision based on that information.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/29117162

 

https://www.ncbi.nlm.nih.gov/pubmed/27321955

 

https://www.ncbi.nlm.nih.gov/pubmed/28583312

 

https://www.ncbi.nlm.nih.gov/pubmed/24476821

 

https://www.ncbi.nlm.nih.gov/pubmed/28988769

 

https://www.ncbi.nlm.nih.gov/pubmed/28753430

 

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New Treatment in Development for Glioblastoma: Hopes for Sen. John McCain

Reporter: Aviva Lev-Ari, PhD, RN

We wish all patients diagnosed with Glioblastoma to be able to benefit from the advancements in Sciences reported, below

SOURCE

Glioblastoma Is A Grim Diagnosis, But There Are Some Signs Of Hope

Karen Weintraub, July 20, 2017 Updated July 21, 2017 5:33 PM

 

Advancements in Crossing The Blood-Brain Barrier

Paula Hammond, of MIT’s Koch Institute of Integrative Cancer Research: “We believe we have a handle on a good stealth mechanism. Now, we’re looking at enhanced uptake,” she said. “We have to begin to think a little bit about how to get nature on our side on this one.”

At the Brigham, researchers are trying another approach to getting across the blood-brain-barrier: prying open holes in its armor with beams of ultrasound. Although normally used to take cool pictures during pregnancy, multiple beams of ultrasound aimed at the same area can make blood vessels of the brain “leakier,” according to research at the Brigham.

 

Advancement in Stem Cells against Tumors

There’s also a possibility that stem cells may be useful for tracking down and killing tumor cells. Khalid Shah, director for the Center for Stem Cell Therapeutics and Imaging at Brigham and Women’s Hospital, has been experimenting with delivering engineered stem cells directly to tumor sites after surgery.

William Curry at Mass. General, is that the longer a patient with glioblastoma can hang on, the better their chances of getting one of these new treatments.

“The longer you stay alive and the longer you maintain good neurological function, the more eligible you one may be to see the benefits and the fruits of a lot of the research that is really accelerating right now,” he said.

SOURCE

Glioblastoma Is A Grim Diagnosis, But There Are Some Signs Of Hope

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Standard of care for localization of impalpable breast lesions, aka Magseed, @ UCSF as First Adopter

Reporter: Aviva Lev-Ari, PhD, RN

PRESS RELEASE

23rd January 2017

  

UCSF first to adopt Magseed as standard of care for localization of impalpable breast lesions

Magseed technology guides surgeons during a breast lumpectomy to simplify treatment and improve patient experience

 

Cambridge, UK & San Francisco, CA, 23rd January 2017: Endomag, the cancer healthcare company, announced today that the University of California, San Francisco (UCSF) has become the first US site to adopt Magseed™ as its standard of care for localization of impalpable breast lesions. Magseed™ is a simpler, more effective alternative to traditional wire localization methods.

 

Breast cancer is the most common form of cancer in women, with 1.7 million new cases of breast cancer globally every year, and is expected to double by 2030. Due to a rise in national screening programmes and an increase in public awareness, breast cancer is being caught at an earlier stage meaning that the tumors are smaller, less defined and harder to feel, with as many as 50% of all breast tumors impalpable at the time of diagnosis. In these cases, a technique called wire localization is typically used by surgeons to locate the tumor.

 

Although widely used, wire localization commonly causes complications. On average 1 in every 4 breast wire localizations result in cancerous tissue being left behind and requiring additional surgery because the wire has become dislodged between when it was implanted and when it was removed during surgery. Additionally, there is a risk of infection due to the wire protruding from the skin, so the placement of the wire must be done on the same day as surgery. These issues result in unnecessary anxiety for patients, delays to the surgical lists and fewer patients being treated as a consequence.

 

Dr. Eric Mayes, CEO of Endomag noted “The wire localization technique has remained largely the same since it was introduced over 30 years ago and it causes a lot of anxiety for patients. We wanted to create a technique that could simplify the localization process and improve the patient experience.”

 

Magseed™ is smaller than a grain of rice and can be placed into the tumor for up to 30 days, allowing the patient to return home ahead of surgery. Once implanted, the seed is not easily dislodged and patients are not restricted in movement or activity. During surgery the seed is detected with the Sentimag® probe to guide accurate removal of the tumor and maximising the amount of healthy tissue left behind. Unlike radioactive alternatives that involve strict regulatory oversight and complex logistics, the Magseed™ technique can be widely adopted by any hospital, regardless of size.

 

Dr. Laura Esserman (Breast Surgeon, UCSF) “We are excited to have a set of safe, easy to use tools that will improve the efficiency of identifying breast lesions and dramatically improve the experience of patients and clinicians, as well as the workflow in the operating room.”

 

 

Dr. Michael Alvarado (Breast Surgeon, UCSF) “We have been looking for a better alternative to wire localization for some time, as the wire procedure adds additional stress for the patients on the day of surgery and often causes delays to our operating schedule. Very early in our evaluation of the magnetic seed technique we found that we could avoid a same-day placement, and the surgeries could be completed in less time, without compromising accuracy. This offers a tangible benefit to both our clinical team and, most importantly, our patients.”

 

ENDS

 

Photo: X-ray showing a complete surgical specimen with negative margins and Magseed™ in the centre, next to the cancer.

For a high res image please contact lorna.cuddon@zymecommunications.com

 

For further information please contact:

Zyme Communications

Lorna Cuddon

Tel: +44 (0)7811 996 942

Email: lorna.cuddon@zymecommunications.com

 

About Endomag http://www.endomag.com 

Endomag is a pioneer in the use of magnetism for minimally-invasive surgical guidance.  By addressing unmet needs in availability, affordability and workflow efficiency for surgical oncology, we support our mission to improve the global standard of cancer care for everyone, everywhere.

 

Founded as a spin-out from the University of Houston and the University College London (UCL) in 2007, we continue to develop our unique clinical platform that uses magnetic fields to power diagnostic and therapeutic devices.  The company has sales in over 30 countries worldwide and is headquartered in Cambridge, United Kingdom.

 

UC Disclaimer

The information stated above was prepared by Endomag, and reflects solely the opinion of the corporation. Nothing in this statement shall be construed to imply any support or endorsement of Endomag, or any of its products, by The Regents of the University of California, its officers, agents and employees.

SOURCE

From: Lorna Cuddon <lorna.cuddon@zymecommunications.com>

Reply-To: <lorna.cuddon@zymecommunications.com>

Date: Monday, January 23, 2017 at 9:16 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: UCSF first to adopt Magseed as standard of care for localization of impalpable breast lesions

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Prostate Cancer Patient: Consider Monitoring vs Surgery or Radiation, only if Life Expectancy is less than a Decade

Reporter: Aviva Lev-Ari, PhD, RN

Boldface by ALA

 

Rethinking Prostate Cancer, in THE MOST NOTABLE MEDICAL FINDINGS OF 2016

For many years, American physicians have screened their older male patients for prostate cancer by looking at the level of a particular protein in the blood. The protein, called prostate-specific antigen (P.S.A.), can indicate the presence of a tumor long before any symptoms materialize. Recently, though, there has been a movement within the medical community against P.S.A. testing; since prostate cancers typically grow very slowly and rarely cause discomfort, the thinking goes, early screening may not be all that useful. The U.S. Preventive Services Task Force, based on data from two large clinical trials, currently recommends against routine screening, but other expert groups (using the same evidence) have countered that men should be allowed to choose for themselves.

Now the dispute has become even more fraught. In October, The New England Journal of Medicine published a study by a group of British researchers that examined three classes of prostate-cancer patients: those who had received surgery, those who had received radiation therapy, and those whose disease had been carefully monitored without intervention. After ten years, there was no difference in survival rates among the three groups. Active treatment does not change the over-all risk of death, and this was the headline in most news reports. But largely overlooked in the press was that metastases, meaning spread of the cancer beyond the prostate gland to tissues in the pelvis and to bone, occurred three times more frequently in those being monitored than in those who received surgery or radiation. Not surprisingly, the cancer also progressed more quickly in these men.

In an editorial that accompanied the study, Anthony D’Amico, a radiation oncologist at Boston’s Dana-Farber Cancer Institute, argued that men should be informed of the risk of metastasis and of its consequences, particularly pelvic tumors and bone pain and fracture. D’Amico advises that men who wish to avoid metastases should consider monitoring, rather than surgery or radiation, only if their life expectancy is less than a decade. Having cared for many men with prostate cancer that metastasized—an incurable situation often marked by severe suffering—I strongly concur.

SOURCE

http://www.newyorker.com/tech/elements/the-most-notable-medical-findings-of-2016?mbid=nl_TNY%20Template%20-%20With%20Photo%20(122)&CNDID=22119822&spMailingID=10139434&spUserID=MTMzMTc5ODE3NDQwS0&spJobID=1062494562&spReportId=MTA2MjQ5NDU2MgS2

 

REFERENCES

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer

Freddie C. Hamdy, F.R.C.S.(Urol.), F.Med.Sci., Jenny L. Donovan, Ph.D., F.Med.Sci., J. Athene Lane, Ph.D., Malcolm Mason, M.D., F.R.C.R., Chris Metcalfe, Ph.D., Peter Holding, R.G.N., M.Sc., Michael Davis, M.Sc., Tim J. Peters, Ph.D., F.Med.Sci., Emma L. Turner, Ph.D., Richard M. Martin, Ph.D., Jon Oxley, M.D., F.R.C.Path., Mary Robinson, M.B., B.S., F.R.C.Path., John Staffurth, M.B., B.S., M.D., Eleanor Walsh, M.Sc., Prasad Bollina, M.B., B.S., F.R.C.S.(Urol.), James Catto, Ph.D., F.R.C.S.(Urol.), Andrew Doble, M.S., F.R.C.S.(Urol.), Alan Doherty, F.R.C.S.(Urol.), David Gillatt, M.S., F.R.C.S.(Urol.), Roger Kockelbergh, D.M., F.R.C.S.(Urol.), Howard Kynaston, M.D., F.R.C.S.(Urol.), Alan Paul, M.D., F.R.C.S.(Urol.), Philip Powell, M.D., F.R.C.S., Stephen Prescott, M.D., F.R.C.S.(Urol.), Derek J. Rosario, M.D., F.R.C.S.(Urol.), Edward Rowe, M.D., F.R.C.S.(Urol.), and David E. Neal, F.R.C.S., F.Med.Sci., for the ProtecT Study Group*

N Engl J Med 2016; 375:1415-1424 October 13, 2016 DOI: 10.1056/NEJMoa1606220

 

Treatment or Monitoring for Early Prostate Cancer

Anthony V. D’Amico, M.D., Ph.D.

N Engl J Med 2016; 375:1482-1483 October 13, 2016 DOI: 10.1056/NEJMe1610395

CITING ARTICLES

  1. Matthew R. Cooperberg. . (2016) Re: 10-Year Outcomes After Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. European Urology.
    CrossRef

  2. Jean-Jacques Mazeron. . (2016) Cancer de la prostate : to treat or not to treat ?. Bulletin du Cancer.
    CrossRef

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p53 mutation – Li-Fraumeni Syndrome – Likelihood of Genetic or Hereditary conditions playing a role in Intergenerational incidence of Cancer

 

Reporter: Aviva Lev-Ari, PhD, RN

 

THIS ARTICLE IS RECOMMENDED READING TO ALL OUR e-Readers

because it is a REAL story of a high school student fighting Brain Cancer, glioblastoma multiforme (GBM)

it presents the FRONTIER OF GENOMICS, PRECISION MEDICINE, Interventional Radiology and Interventional ONCOLOGY at

Stanford University, Canary Center at Stanford for Early Cancer Detection, Stanford Medical Center and Lucile Packard Children’s Hospital

I was exposed to Li-Fraumeni Syndrome in the following article:

‘And yet, you try’ – A father’s quest to save his son

http://stanmed.stanford.edu/2016fall/milan-gambhirs-li-fraumeni-syndrome.html

 

Li-Fraumeni syndrome

Other Names for This Condition

  • LFS
  • Sarcoma family syndrome of Li and Fraumeni
  • Sarcoma, breast, leukemia, and adrenal gland (SBLA) syndrome
  • SBLA syndrome

LFS is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.

The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called

Soft tissue sarcoma forms in soft tissues of the body, including muscle, tendons, fat, blood vessels, lymph vessels, nerves, and tissue around joints.


(small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.

A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.

Genetic Changes

The CHEK2 and TP53 genes are associated with Li-Fraumeni syndrome.

More than half of all families with Li-Fraumeni syndrome have inherited mutations in the gene. TP53 is a tumor suppressor gene, which means that it normally helps control the growth and division of cells. Mutations in this gene can allow cells to divide in an uncontrolled way and form tumors. Other genetic and environmental factors are also likely to affect the risk of cancer in people with TP53 mutations.

A few families with cancers characteristic of Li-Fraumeni syndrome and Li-Fraumeni-like syndrome do not have TP53 mutations, but have mutations in the CHEK2 gene. Like the TP53 gene, CHEK2 is a tumor suppressor gene. Researchers are uncertain whether CHEK2 mutations actually cause these conditions or are merely associated with an increased risk of certain cancers (including breast cancer).

Inheritance Pattern

Li-Fraumeni syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing cancer. In most cases, an affected person has a parent and other family members with cancers characteristic of the condition.

Diagnosis and Management

These resources address the diagnosis or management of Li-Fraumeni syndrome:

References on LFS

SOURCE

https://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome

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